Bacterial Prostatitis

REVIEW

CURRENT OPINION Bacterial prostatitis

Bradley C. Gill a,b and Daniel A. Shoskesa,b

Purpose of review The review provides the infectious disease community with a urologic perspective on bacterial prostatitis. Specifically, the article briefly reviews the categorization of prostatitis by type and provides a distillation of new findings published on bacterial prostatitis over the past year. It also highlights key points from the established literature. Recent findings Cross-sectional prostate imaging is becoming more common and may lead to more incidental diagnoses of acute bacterial prostatitis. As drug resistance remains problematic in this condition, the reemergence of older antibiotics such as fosfomycin, has proven beneficial. With regard to chronic bacterial prostatitis, no clear clinical risk factors emerged in a large epidemiological study. However, bacterial biofilm formation has been associated with more severe cases. Surgery has a limited role in bacterial prostatitis and should be reserved for draining of a prostatic abscess or the removal of infected prostatic stones. Summary Prostatitis remains a common and bothersome clinical condition. Antibiotic therapy remains the basis of treatment for both acute and chronic bacterial prostatitis. Further research into improving prostatitis treatment is indicated. Keywords acute bacterial prostatitis, bacterial prostatitis, category I prostatitis, category II prostatitis, chronic bacterial prostatitis, male pelvic pain

INTRODUCTION and August 2015 were identified among the first Prostatitis is a bothersome condition but carries 600 search results. The titles of English language potential for serious morbidity from sepsis, abscess, articles were examined and those pertaining to non- or fistula if insufficiently managed. Nearly one in six bacterial prostatitis, chronic pelvic pain, and animal men report a history of prostatitis, resulting in over or basic science models were excluded. After this, a $84 million in annual medical expenditure [1,2]. total of 38 articles related to acute and chronic Prostatitis exhibits a bimodal peak of incidence, bacterial prostatitis were reviewed. with men between 20 and 40 years of age or older than 60 years afflicted most commonly [3]. The Prostatitis categorization scheme reasons for this distribution or potential for con- The National Institutes of Health consensus classi- founding by sexually transmitted infections are fication of prostatitis (Table 1) divides the condition unknown. In over 90% of men with fever and uri- into four categories based upon clinical presentation nary symptoms, prostatitis is the underlying con- [7]. These include acute (category I) and chronic dition in the absence of pyelonephritis symptoms (category II) bacterial prostatitis, as well as chronic [4]. With that, prostatitis accounts for nearly 8% of prostatitis/pelvic pain syndrome (category III) and urologist visits [5]. Overall, prostatitis remains a common condition and research to improve its a management would be beneficial. Department of Urology, Glickman Urological and Kidney Institute and bLerner College of Medicine, Education Institute, Cleveland Clinic, This review provides a distillation of notable Cleveland, Ohio, USA additions to the literature on prostatitis over the Correspondence to Daniel A. Shoskes, MD, Department of Urology, past year. It builds upon the journal’s February 2014 Glickman Urological and Kidney Institute, Cleveland Clinic, Mail Stop & review [6 ]. Additionally, it provides a brief overview Q10–1, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel: +1 216 of prostatitis categorization. To complete this manu- 445 4757; fax: +1 216 444 0390; e-mail: [email protected] script, a PubMed query for ‘prostatitis’ was con- Curr Opin Infect Dis 2016, 29:86–91 ducted and articles dated between January 2014 DOI:10.1097/QCO.0000000000000222 www.co-infectiousdiseases.com Volume 29 Number 1 February 2016 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Bacterial prostatitis Gill and Shoskes

(dysuria, urinary frequency, and urinary urgency), KEY POINTS and focal symptoms (pelvic or perineal pressure) Tailoring antibiotic treatment to culture-proven bacterial suggestive of prostatic involvement. Obstructive sensitivity is essential. urinary symptoms (weak stream, dribbling, and hesitancy) may also present, with urinary retention Any chosen antibiotic must penetrate the prostate and possible. Commonly, an intervention such as trans- reach therapeutic levels. rectal ultrasound-guided prostate biopsy may Antibiotic resistance is increasingly problematic. precede presentation. A sexual history may indicate the risk of a sexually transmitted infection. The indications for surgery in managing prostatitis Rectal examination almost always shows a ten- remain limited and very specific. der prostate. However, caution is warranted during digital rectal examination, as aggressive prostate palpation can release bacteria and inflammatory asymptomatic inflammatory prostatitis (category cytokines triggering an abrupt clinical decompensa- IV). To date, no data support the role of ‘hidden’ tion, thus contraindicating prostatic massage. infection or atypical organisms in category III or IV Serum laboratory assessment in CIP generally prostatitis. As such, there is no role for antibiotic reveals leukocytosis. During infection, prostate- therapy in these conditions, despite many patients specific antigen is invariably elevated and has no strongly believing a true infection exists and seeking diagnostic value for prostate cancer. Urinalysis and out multiple practitioners to diagnose one. urine culture are essential and blood cultures are indicated for a clinical suspicion of sepsis. All men should have a postvoid residual urine volume CATEGORY I PROSTATITIS: ACUTE measurement, as urinary retention may not be evi- BACTERIAL PROSTATITIS dent. Imaging with computed tomography (CT) Acute bacterial prostatitis or National Institutes of scan or ultrasound may reveal an enlarged and Health category I prostatitis (CIP) is defined as an inflamed heterogeneously appearing prostate, but acute urinary tract infection (UTI) with prostatic is not necessary unless concern for prostatic abscess involvement. Patients are usually febrile and may exists. present with urinary retention. Infection results from bacteria ascending the urethra, reflux of con- taminated urine into the prostatic ducts, direct Treatment introduction of bacteria during transrectal biopsy Successful treatment of CIP rests upon completion or urethral instrumentation, or hematogenous seed- of a sufficient course of appropriate antibiotic. The ing. Causative organisms include Escherichia coli in agent used must have demonstrated sensitivity most (65–80%) cases with Pseudomonas aeruginosa, against the infecting organism and also reach thera- Proteus mirabilis, Klebsiella spp., Serrita, and Enter- peutic levels in the prostate. During acute infection obacter spp. comprising the remainder [8–10]. With with prostatic inflammation, most antibiotics do impaired immunity, other microorganisms like penetrate the prostate (except nitrofurantoin) fungi (Cryptococcus spp. or Histoplasma spp.) and [11]. Without evidence of systemic disease or uri- Gram-positive (skin flora) bacteria, as well as Myco- nary retention, an oral antibiotic for 2–4 weeks is bacterium tuberculosis may be implicated. generally sufficient. Typical agents include a fluoroquinolone or trimethoprim-sulfamethoxazole, Diagnosis with the quinolones reaching 3–4 times higher Men typically present with systemic symptoms intraprostatic concentrations than beta-lactam anti- (malaise, fevers, chills, and sweats), evidence of UTI biotics [10]. Repeat urine culture during therapy to assess for bacterial eradication is necessary, if clinical Table 1. National Institutes of Health consensus definition improvement is not seen, however, all cases of CIP and classification of prostatitis should have a confirmatory urine culture about 1 week following antibiotic completion to ensure National Institutes of Health consensus definition and bacteriologic cure. classification of prostatitis The acutely ill patient warranting hospitaliz- Category I Acute bacterial prostatitis ation for prostatitis will present a clinical picture Category II Chronic bacterial prostatitis of sepsis or a systemic inflammatory response syn- Category III Chronic prostatitis/chronic pelvic pain syndrome drome. Urinary tract decompression is often Category IV Asymptomatic inflammatory prostatitis required for urinary retention with grossly infected urine via a short-term indwelling urethral catheter,

0951-7375 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved. www.co-infectiousdiseases.com 87 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Urinary tract infections clean intermittent urethral catheterization, or a Urologic procedures may incite UTIs and pros- suprapubic catheter. Parenteral antibiotic therapy tatitis. A case report detailed a case of Salmonella is indicated until clinical stabilization is achieved, typhimurium prostatitis in a spinal cord injury with the chosen regimen guided by local anti- patient performing clean intermittent urethral biogram results. Typical treatment consists of catheterization and discussed the role of perineal empiric broad coverage with a fluoroquinolone colonization and bacterial seeding in such a setting and aminoglycoside, possibly in combination with [19]. A comparison of the clinical details in a series of a penicillin or cephalosporin (second/third gener- CIP after transrectal prostate biopsy described a ation). Based upon blood and urine culture results, a higher incidence of sepsis and antibiotic-resistant transition to oral antibiotics can be completed. bacteria in the postbiopsy prostatitis group [20&&]. Additional treatments to address pain, inflam- Current guidelines recommend under 24 h of mation, and anatomic complications may be periprocedural antibiotic prophylaxis for prostate warranted in some patients. In instances of persist- biopsy [21]. Another series noted all cases of post- ent or very slowly improving CIP, the presence of biopsy prostatitis were caused by drug-resistant prostatic abscess must be considered. Cross-sec- E. coli and treatment with an intravenous third- tional imaging with CT can be helpful identifying generation cephalosporin or imipenem was effec- an abscess and facilitating transurethral or trans- tive for these [22]. A comparative analysis of trans- perineal drainage. A transrectal ultrasound may rectal and transurethral procedures found similar also identify prostatic abscesses, and if done under results, but Pseudomonas spp. were far more com- anesthesia, can accommodate concomitant trans- mon in transurethral procedures [23&]. rectal drainage. The pain and discomfort accompa- Lastly, several case reports on CIP were recently nying prostatitis is thought to stem from local published. One was that of a Stapylococcus aureus inflammation. The use of nonsteroidal anti- prostatic abscess diagnosed by CT and MRI in an inflammatory medications can markedly reduce immunocompetent host with the classic clinical prostatitis-related pain [12]. In addition, the admin- picture of persistent prostatitis and worsening infec- istrationofanalfa-1-adrenergicantagonisthas tious symptoms [24]. The remaining reports high- also been found to aid in prostatitis-related lower lighted acute Coccidioides fungal prostatitis and urinary tract symptom relief [13]. acute Raoultellaplanticola bacterial prostatitis in hosts immune compromised secondary to cortico- steroids and immunosuppression for renal trans- New developments plant, respectively [25,26]. A review on diagnosis Several reports of imaging in prostatitis have and treatment of prostatic tuberculosis, with an recently been published, likely secondary to emphasis on drug-resistance in Eastern Europe increases in the use of multiparametric MRI for and Central Asia, was also completed [27]. prostate cancer diagnosis and active surveillance. A description of Bacillus Calmette–Guerin (BCG) granulomatous prostatitis, secondary to BCG CATEGORY II: CHRONIC BACTERIAL therapy for bladder cancer, highlighted nearly PROSTATITIS identical imaging characteristics of this condition Recurrent UTIs with the same organism suggest a and prostate cancer [14]. Another study detailed the persistent source of urinary tract bacterial seeding. imaging characteristics that differentiate the lesions Chronic bacterial prostatitis or category II prostatitis [15]. Subsequently, a review of MRI findings in acute (CIIP) is defined as recurrent UTIs with the same and chronic prostatitis, as well as prostate cancer, organism in prostatic secretions during asympto- detailed the challenges of discriminating between matic periods [7]. Only 10% of men with CIP will these clinical entities [16&]. Reports of radiotracer eventually develop CIIP [28]. Similarly, CIIP com- imaging in prostatitis were also published, with one prises just 10% of all prostatitis cases [29]. CIIP may describing positron emission tomography (PET)/CT also impair fertility per its association with impaired to diagnose and observe CIP resolution [17]. A sep- semen quality and a higher prevalence of premature arate report noted incidental cases of BCG granu- ejaculation with Chlamydia trachomatis infection lomatous prostatitis on PET/CT and reviewed typical [30,31]. Causative organisms include E. coli in most PET/CT findings in acute prostatitis [18]. Taken cases with P. aeruginosa, P. mirabilis, Klebsiella spp., together, these new reports of imaging in prostatitis and Enterobacter spp. leading to others [32]. suggest the incidence of its incidental detection may increase as prostate MRI becomes more common, Diagnosis although true CIP presents as a symptomatic A recent consensus guideline reviews patient evalu- condition. ation and management in CIIP [33&&]. The history is

88 www.co-infectiousdiseases.com Volume 29 Number 1 February 2016 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Bacterial prostatitis Gill and Shoskes that of intermittent symptomatic episodes that New developments resemble CIP, but generally without fever, which Clarifying risk factors for CIIP may improve its treat- resolve with antibiotic treatment. The crux of CIIP ment. A large epidemiological analysis using the diagnosis is the ‘two glass test,’ where a clean catch Health Professionals Follow-Up Study cohort found urine specimen is obtained prior to examination no associations between lifestyle risk factors and and a second specimen of expressed prostatic chronic prostatitis/chronic pelvic pain syndrome secretions is collected during prostatic massage or [42&]. Although in a group of 50 chronic spinal cord within the first urination following this [34]. These injury patients, asymptomatic bacterial prostatitis specimens are then sent for culture to screen for was unrelated to recurrent UTIs upon routine infection and identify the causative agent. No hard urologic evaluation [43]. An investigation of rapid evidence exists for a diagnostic cutoff in colony diagnosis using prostatic fluid leukocyte CD64 count for symptomatic patients. Semen or ejaculate expression compared to bacterial cultures showed culture may increase the number of bacteria promise in expediting laboratory confirmation of detected, but decreases the specificity for true uro- prostatitis per the authors’ interpretation of the data pathogens secondary to skin contaminants [35]. [44]. Transrectal ultrasound may be helpful to identify High recurrence rates suggest incomplete heavy prostatic calcification, which may serve as a bacterial elimination occurs with CIIP treatment. nidus for recurrent infection. In 34 spinal cord injury patients with CIIP only two had bacterial eradication [45]. This suggests interventions should be limited to symptomatic Treatment cases. Certain bacterial virulence factors may pre- The basis of CIIP treatment is antibiotics. Unlike dispose to persistent prostatic infection. One study CIP, the ability of antibiotics to penetrate the cultured prostatic bacterial isolates for quantitative noninflamed prostate is crucial in drug selection. assessment of biofilm production and found biofilm Generally, antibiotics with a high pKa (acid dis- producing bacteria were positively associated with sociation constant) and increased lipid solubility symptom severity and negatively with improve- have superior prostatic penetration. The quino- ment upon treatment [46&&]. Another study ident- lones, sulfas, macrolides, and tetracyclines typically ified seminal vesiculitis using single photon exhibit these features [36]. If indicated, sexually emission computerized tomography and found transmitted infection with C. trachomatis, should typical CIIP organisms in percutaneous aspirates be treated [37]. In all cases, the optimal duration [47&]. This suggests the seminal vesicles may seques- of antibiotics is at least 2–4 weeks, with up to ter bacteria causing recurrent prostatic infections. 6 weeks or repeated treatment courses often needed Antibiotics remain the foundation of CIIP treat- [32,38]. However, despite prolonged administration ment. The tolerability and efficacy of daily 500 mg of optimal agents, a 25–50% recurrence rate exists levofloxacin for 4 weeks was recently validated in [39,40]. If the source of prostatic infection cannot be Saudi Arabian patients [48]. The comparative effec- eliminated, long-term low-dose antibiotic therapy tiveness of the newer macrolide roxithromycin may suppress symptomatic recurrences, but long- relative to ciprofloxacin and aceclofenac was also term data on this approach are lacking [32,36]. demonstrated [49]. Nutriceutical supplementation Apart from antibiotic bacterial eradication, non- (Serenoarepens/Lactobacillus sporogens/arbutin) with steroidal anti-inflammatory medications can reduce prulifloxacin antibiotic therapy was found to be discomfort and local symptoms. Additionally, there superior to the antibiotic alone for bacteriologic are some data that alfa-1-adrenergic antagonists cure and symptoms [50]. Otherwise, rifaximin with may expedite symptom resolution and reduce bac- probiotic VSL#3 was found superior to no treatment teriologic recurrence [41]. Given the often frequent for reducing the progression of bacteriologically and prolonged antibiotic courses, the authors feel cured CIIP in men with irritable bowel syndrome, probiotic use may reduce the risk of antibiotic- based upon the benefit of probiotics observed in the related diarrhea. The role for surgery in CIIP is latter condition [51]. limited. The transurethral elimination of prostatic A pair of case reports on drug-resistant bacterial tissue, by various techniques, may resolve elevated prostatitis treated with fosfomycin detailed the postvoid residual urine volumes and eradicate bac- related pharmacokinetics of each [52]. Commentary teria-harboring intraprostatic stones, removing accompanying this provided insight into using fos- these risks for infection. Otherwise, in very rare fomycin for UTI [53]. Another study assessed intra- situations, where recurrent life-threatening sepsis prostatic, urinary, and serum concentrations of develops, radical prostatectomy, which includes fosfomycin after oral administration, which ident- seminal vesicle removal, can be discussed. ified reasonable levels in the normal prostate

0951-7375 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved. www.co-infectiousdiseases.com 89 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Urinary tract infections without inflammation [54&&]. A similar study 6. Wagenlehner FM, Weidner W, Pilatz A, Naber KG. Urinary tract infections and & bacterial prostatitis in men. Curr Opin Infect Dis 2014; 27:97–101. described the pharmacokinetics and pharmacody- The reference is the prior year’s review of bacterial prostatitis. It provides a relative framework for this year’s article and the new findings that have been published. namics of piperacillin–tazobactam by measuring 7. Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus definition and classification serum and prostate tissue levels at transurethral of prostatitis. JAMA 1999; 282:236–237. 8. Schneider H, Ludwig M, Hossain HM, et al. The 2001 Giessen Cohort Study prostate resection [55]. 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